Asthma in Adults

1. Clinical Features:
   • Variable and recurring symptoms, including wheezing, shortness of breath, chest tightness, and cough.
   • Symptoms can vary in intensity and are often worse at night or early morning.
   • Episodes may be triggered by allergens, irritants, exercise, infections, or stress.
2. Physiological Characteristics:
   • Reversible airway obstruction, either spontaneously or with treatment.
   • Bronchial hyperresponsiveness (airways overly sensitive to various stimuli).
3. Pathological Basis:
   • Chronic inflammation involving multiple cells and mediators, including mast cells, eosinophils, T-lymphocytes, and neutrophils.
     
     

1. NAEPP (National Asthma Education and Prevention Program):
   • Describes asthma as a common, chronic airway disorder characterised by variable symptoms, airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation. It emphasises the interaction of these features in determining disease severity and treatment response.
2. GINA (Global Initiative for Asthma):
   • Defines asthma as a heterogeneous disease, generally marked by chronic airway inflammation. Key features include a history of respiratory symptoms (e.g., wheeze, shortness of breath) and variable expiratory airflow limitation.
     
     

Genetic Factors

1. Genetic Predisposition:
   • Asthma is linked to multiple genetic loci, including ADAM33, IL1RL1, GSDMB, and chromosome 12q. Polymorphisms in tumor necrosis factor and the vitamin D receptor are also implicated.
   • Specific genotypes influence susceptibility to asthma and responsiveness to treatments.
2. Cytokine Imbalance:
   • Dysregulation of Th1 and Th2 cytokines may contribute to allergic inflammation. An excessive Th2 response is associated with asthma development.
3. Gene-Environment Interactions:
   • Host genetic susceptibility interacts with environmental exposures to promote airway hyperresponsiveness and inflammation.

Environmental Triggers

1. Allergens and Irritants:
   • Common allergens include dust mites, animal dander (e.g., cats, dogs), cockroach allergens, and fungi. Irritants such as household sprays, paint fumes, and volatile organic compounds exacerbate symptoms.
2. Respiratory Infections:
   • Viral infections like rhinovirus, respiratory syncytial virus (RSV), and human metapneumovirus are significant contributors, especially in early life. Bacterial infections such as Mycoplasma pneumoniae and Chlamydia pneumoniae also play a role.
3. Pollutants and Smoking:
   • Indoor air pollutants from cooking, wood burning, and natural gas increase asthma risk. Tobacco smoke and vaping further exacerbate symptoms by increasing neutrophilic inflammation and obstructive lung function impairment.
4. Occupational Exposures:
   • Occupational asthma accounts for 10-15% of adult cases, with exposure to chemicals, dust, and allergens in workplaces like farming and plastics manufacturing.
5. Medications:
   • Aspirin-induced asthma occurs in individuals with sensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) and is linked to increased eosinophils and leukotrienes.
     
     

Physiological and Lifestyle Contributors

1. Obesity:
   • Obesity is associated with increased airway inflammation and reduced asthma control. Sustained weight loss improves outcomes.
2. Gastroesophageal Reflux Disease (GERD):
   • Acid reflux exacerbates asthma by increasing airway reactivity through neural reflexes. Approximately 64% of asthma patients show improvement with antireflux therapy.
3. Emotional and Physical Stress:
   • Stress and strong emotions may trigger asthma exacerbations. Exercise-induced asthma is common in both athletes and individuals with heightened airway sensitivity.
4. Socioeconomic Disparities:
   • Poor living conditions, reduced healthcare access, and psychosocial stress disproportionately affect socioeconomically disadvantaged populations, leading to worse asthma outcomes.
     
     

1. Airway Inflammation:
   • Primary Mechanisms:
     • Inflammation is initiated by the activation of dendritic cells, which present antigens to naïve T cells, driving a Th2-dominant immune response.
     • This response involves cytokines such as IL-4, IL-5, and IL-13, which mediate IgE production, eosinophil recruitment, and mucus hypersecretion.
   • Inflammatory Mediators:
     • Leukotrienes (e.g., LTB4), prostaglandins (e.g., PGD2), and histamines released from mast cells amplify airway narrowing and edema.
     • Chemokines such as eotaxin recruit eosinophils to the site of inflammation, exacerbating tissue damage.
2. Bronchial Hyperresponsiveness (AHR):
   • Fixed AHR: Persistent airway changes caused by structural remodeling, including smooth muscle hypertrophy and fibrosis.
   • Variable AHR: Episodic narrowing driven by acute inflammatory responses, often triggered by allergens or irritants.
   • Increased airway smooth muscle contractility and heightened sensitivity to irritants distinguish asthmatic airways from healthy ones.
3. Airflow Obstruction:
   • Caused by a combination of acute and chronic changes:
     • Acute bronchoconstriction: Immediate narrowing due to mast cell degranulation.
     • Mucus hypersecretion: Excessive production of mucins, forming plugs that block airways.
     • Airway edema: Swelling from vascular leakage during late-phase responses.
   • Chronic airflow obstruction may result from airway remodeling, leading to reduced reversibility.
     
     

Cellular and Molecular Mechanisms

1. Immune Cells Involved:
   • Eosinophils: Play a central role in type 2 inflammation, releasing cytotoxic proteins (e.g., major basic protein) that damage the airway epithelium.
   • Mast Cells: Release histamine, tryptase, and prostaglandins during degranulation, contributing to bronchoconstriction and vascular permeability.
   • Neutrophils: Predominantly observed in severe asthma and near-fatal exacerbations, they amplify inflammation through protease release.
   • Invariant Natural Killer (NK) T Cells: Contribute to airway inflammation by releasing cytokines and bridging innate and adaptive immunity.
2. Cytokine Imbalance:
   • The dominance of Th2 cytokines (e.g., IL-4, IL-5, IL-13) over Th1 cytokines skews the immune response, driving allergic inflammation.
   • IL-13 also plays a pivotal role in airway remodeling, promoting fibrosis and goblet cell hyperplasia.
     
     

Structural Changes and Airway Remodeling

• Epithelial Damage:
  • Sloughing of epithelial cells exposes the underlying basal layer, contributing to airway hyperreactivity.
  • Creola bodies, clumps of epithelial cells in sputum, are indicative of epithelial shedding.
• Basement Membrane Thickening:
  • Collagen deposition beneath the epithelium, leading to increased airway stiffness.
• Smooth Muscle Changes:
  • Hypertrophy and hyperplasia increase airway wall thickness, reducing luminal diameter and amplifying bronchoconstriction.
• Mucus Gland Hyperplasia:
  • Excessive mucus production, often containing mucins, contributes to airway plugging observed in severe asthma.

Environmental and Physiological Influences

1. Triggers:
   • Allergens (e.g., pollen, dust mites) and irritants (e.g., smoke, pollutants) directly activate immune pathways.
   • Viral infections (e.g., rhinovirus, RSV) can exacerbate inflammation and airway hyperresponsiveness.
2. Hygiene Hypothesis:
   • Suggests that reduced microbial exposure in early life predisposes individuals to Th2-skewed immunity, increasing asthma susceptibility.
3. Vascular and Neural Factors:
   • Airway inflammation alters autonomic neural control, increasing parasympathetic tone and promoting bronchoconstriction.
     
     

Pathophysiological Progression

1. Early-Phase Reaction:
   • Triggered within minutes of allergen exposure by mast cell degranulation and mediator release, leading to acute bronchoconstriction.
2. Late-Phase Reaction:
   • Occurs hours later, characterised by eosinophil and mononuclear cell infiltration, contributing to sustained inflammation and edema.
3. Chronic Changes:
   • Prolonged inflammation results in irreversible remodeling, with significant impact on airway function and asthma control.
     
     

Clinical Implications

• Airway inflammation and remodeling contribute to airflow limitation, hyperinflation, and ventilation-perfusion mismatch.
• Severe asthma phenotypes may exhibit distinct inflammatory profiles, necessitating tailored therapeutic strategies.
  
  

Global Prevalence

1. Worldwide Burden:
   • In 2019, the global asthma burden was estimated at 262 million cases, with approximately 250,000 asthma-related deaths annually.
   • The World Health Organization (WHO) reports that asthma contributes to the loss of 15 million disability-adjusted life years (DALYs) each year.
2. Regional Variability:
   • The highest prevalence rates are reported in industrialised countries like Australia, Sweden, Canada, and New Zealand.
   • Conversely, lower prevalence rates are seen in countries such as China and Vietnam.
     
     

Asthma in Specific Populations

1. United States:
   • Affects approximately 25 million individuals, including 4.7 million children.
   • Prevalence is disproportionately higher among non-Hispanic Black individuals, who also experience higher morbidity and mortality rates. Hispanic females demonstrate significant lung function deficits.
   • Exercise-induced bronchospasm affects 12–15% of the general population with underlying asthma.
2. United Kingdom:
   • In 2019/2020, asthma prevalence was 6.5%, affecting 5.4 million individuals, including around 200,000 cases of severe asthma.
3. Demographic Trends:
   • Asthma predominantly affects boys during childhood (male-to-female ratio of 2:1) but becomes more prevalent in females after puberty.
   • The majority of adult-onset asthma cases occur in females over 40 years old.
     
     

Age-Related Prevalence

1. Children and Adolescents:
   • Two-thirds of asthma cases are diagnosed before 18 years of age.
   • About 50% of children with asthma experience a reduction or resolution of symptoms by early adulthood.
2. Older Adults:
   • Prevalence increases among older adults due to reduced lung function and heightened airway responsiveness.
     
     

Urbanisation and Environmental Impact

1. Industrialisation and Urbanization:
   • Higher asthma prevalence in urbanised and industrialised settings is linked to factors such as air pollution, passive smoking, and exposure to environmental allergens.
   • Trends indicate increasing asthma prevalence, especially among children under 6 years of age.
2. Environmental and Socioeconomic Influences:
   • Socioeconomic disparities contribute to unequal access to asthma management, particularly among minority and disadvantaged groups.
   • Urban environments and poor living conditions exacerbate asthma morbidity.
     
     

Key Historical Considerations

1. Assessment of Symptoms:
   • Intermittent wheezing is the hallmark symptom, typically high-pitched and polyphonic, most noticeable during expiration.
   • Cough, often dry and nocturnal, may be the sole manifestation in cases of exercise-induced or nocturnal asthma.
   • Chest tightness or discomfort, described as a band-like constriction or heaviness, frequently accompanies exacerbations.
   • Dyspnea (shortness of breath), triggered by allergens, infections, or physical exertion, can awaken patients at night.
2. Episodic Nature:
   • Symptoms often have a temporal relationship with specific triggers, including allergens (dust mites, pet dander, pollen), irritants (smoke, pollutants), cold air, exercise, and viral infections.
   • Nighttime exacerbations and early morning worsening are common patterns.
3. Triggers and Exacerbation Patterns:
   • Environmental: Household allergens, workplace irritants, and urban pollutants.
   • Lifestyle: Smoking, vaping, and stress can amplify symptoms.
   • Seasonal Changes: Increased symptoms during pollen seasons or cold weather.
4. Exercise-Induced Bronchoconstriction (EIB):
   • Symptoms, such as cough, wheeze, and dyspnea, appear during or shortly after intense exercise.
   • Cold, dry air exacerbates EIB, while warm, humid conditions may alleviate it. Swimming is often better tolerated.
     
     

Personal and Family History

1. Family History:
   • A family history of asthma, eczema, allergic rhinitis, sinusitis, or nasal polyps significantly increases the likelihood of asthma.
2. Personal History of Atopy:
   • Eczema, hay fever, or food allergies are commonly associated with asthma, forming part of the "atopic march."
3. Childhood Respiratory Symptoms:
   • Recurrent bronchitis, wheezy bronchitis, or nocturnal cough during childhood may suggest early-onset asthma.
     
     

Social and Occupational History

1. Environmental Factors:
   • Home characteristics, such as exposure to smoke, pets, or mold, can worsen symptoms.
   • Occupational exposures (e.g., dust, chemicals, animal dander) are implicated in 10-15% of adult-onset asthma cases.
2. Lifestyle Factors:
   • Smoking and vaping exacerbate symptoms and worsen outcomes.
   • Socioeconomic status affects housing quality, access to healthcare, and exposure to environmental stressors.
     
     

Exacerbation History

1. Symptom Patterns:
   • Typical prodromal symptoms, such as nasal congestion or throat irritation, precede exacerbations.
2. Severity Assessment:
   • Frequency of emergency visits, hospitalisations, ICU admissions, and missed school or workdays provides insight into asthma control.
3. Treatment Response:
   • History of response to bronchodilators or corticosteroids helps confirm asthma.
     
     

Distinguishing Features

1. Wheezing Variations:
   • Inspiratory monophonic wheezing (e.g., vocal cord dysfunction) differs from polyphonic expiratory wheezing in asthma.
2. Cough Variants:
   • Chronic or nocturnal cough without infection strongly favors asthma.
3. Non-Asthmatic Causes:
   • Conditions like heart failure, chronic bronchitis, or cystic fibrosis may mimic asthma symptoms.
     
     

Other Notable Factors

1. Aspirin-Exacerbated Respiratory Disease (AERD):
   • A triad of asthma, nasal polyps, and aspirin sensitivity, usually manifesting in adulthood.
2. Comorbidities:
   • Gastroesophageal reflux disease (GERD), obstructive sleep apnea (OSA), and obesity are frequently associated with poorly controlled asthma.
     
     

General Examination Findings

1. Key Pulmonary Findings:
   • Wheezing: High-pitched, musical, polyphonic wheezes, primarily expiratory, but can be biphasic in severe cases.
   • Silent Chest: Absence of wheezing during severe obstruction indicates critical airflow limitation.
   • Prolonged Expiratory Phase: Reduced expiratory flow resulting in a decreased inspiratory-to-expiratory ratio (I:E ratio).
   • Accessory Muscle Use: Engagement of neck (sternocleidomastoid), chest, and abdominal muscles indicates increased respiratory effort.
2. Other Respiratory Signs:
   • Tachypnea: Elevated respiratory rate reflects increased work of breathing.
   • Tripod Position: Patients may lean forward with hands supporting the torso to optimise accessory muscle use.
   • Pulsus Paradoxus: An exaggerated inspiratory drop in systolic blood pressure (>12 mmHg) suggests severe obstruction and respiratory muscle fatigue.
     
     

Extrapulmonary Examination Findings

1. Upper Airway:
   • Nasal Features: Pale, swollen nasal mucosa or cobblestoning indicative of allergic rhinitis.
   • Nasal Polyps: May suggest aspirin-exacerbated respiratory disease (AERD) or require evaluation for cystic fibrosis in children.
2. Dermatologic Signs:
   • Atopic Dermatitis/Eczema: Supports a diagnosis of atopic asthma in children or adolescents.
3. Cardiovascular:
   • Absence of clubbing; its presence should prompt evaluation for alternative diagnoses (e.g., interstitial lung disease or cystic fibrosis).
     
     

Wheezing and Differential Diagnosis

1. Wheezing Specificity:
   • Polyphonic expiratory wheezing is typical of asthma.
   • Inspiratory monophonic wheezing may suggest vocal cord dysfunction or tracheal obstruction.
2. Silent Chest:
   • Represents extreme obstruction with minimal airflow; a medical emergency requiring immediate intervention.
     
     

Additional Examination Notes

1. Infrequent Findings:
   • Peripheral cyanosis and diaphoresis during severe exacerbations.
   • Bradycardia or hypotension in late-stage respiratory failure.
2. Absent Signs:
   • Clubbing is not a feature of asthma; its presence requires further evaluation for other conditions.
     
     

Classification of Examination Findings by Severity

1. Mild Exacerbations:
   • Respiratory rate: Slightly elevated.
   • Wheezing: End-expiratory and moderate.
   • Heart rate: <100 bpm, no pulsus paradoxus.
   • Oxygen saturation: >95% on room air.
   • Posture: Able to lie flat comfortably.
   • Speech: Normal, full sentences.
2. Moderate Exacerbations:
   • Respiratory rate: Significantly elevated with use of accessory muscles.
   • Wheezing: Loud and predominantly expiratory.
   • Heart rate: 100–120 bpm, possible pulsus paradoxus (10–20 mmHg).
   • Oxygen saturation: 91–95% on room air.
   • Posture: Upright, with discomfort lying flat.
   • Speech: Short phrases due to breathlessness.
3. Severe Exacerbations:
   • Respiratory rate: >30 breaths/min.
   • Wheezing: Biphasic, involving both inspiration and expiration, or absent in critical cases ("silent chest").
   • Heart rate: >120 bpm, pulsus paradoxus (20–40 mmHg).
   • Oxygen saturation: <91%.
   • Posture: Tripod position with severe distress.
   • Speech: Single words or inability to speak.
4. Imminent Respiratory Arrest:
   • Paradoxical thoracoabdominal movement due to respiratory muscle fatigue.
   • Cyanosis, bradycardia, or confusion indicating severe hypoxia.
   • Diaphoresis with minimal or no air movement on auscultation.
   • Extreme drowsiness or somnolence suggests hypercapnia.
     
     

First-Line Investigations

1. Spirometry (FEV₁/FVC Ratio and Bronchodilator Reversibility [BDR])
   • Purpose: To identify airflow obstruction and assess reversibility.
   • Parameters:
     • FEV₁/FVC Ratio: A ratio below the lower limit of normal (LLN) or <70% indicates airflow obstruction.
     • Reversibility: An increase in FEV₁ of ≥12% and ≥200 mL post-bronchodilator confirms asthma. An improvement >400 mL strongly suggests asthma.
   • Considerations:
     • Use LLN-based interpretation to avoid overdiagnosing obstruction in older adults.
     • Spirometry may be normal in asymptomatic patients; a false-negative rate of up to 50% necessitates additional tests.
2. Peak Expiratory Flow (PEF) Monitoring
   • Use: Assess variability in airflow over 2–4 weeks.
   • Positive Test: Variability >20% between highest and lowest PEF readings.
   • Notes: Best for monitoring rather than initial diagnosis; relies on patient adherence and effort.
3. Fractional Exhaled Nitric Oxide (FeNO)
   • Purpose: Detect eosinophilic airway inflammation.
   • Positive Test: FeNO levels ≥40 ppb in corticosteroid-naive adults.
   • Limitations:
     • Increased by rhinitis, viral infections, and height.
     • Decreased by smoking and corticosteroid use.
     • Not a definitive test; should be combined with spirometry and clinical judgment.
4. Bronchodilator Reversibility (BDR) Testing
   • Method: Spirometry before and after administration of a short-acting bronchodilator.
   • Positive Test: A change in FEV₁ or FVC >12% or ≥200 mL.
     
     

Second-Line or Additional Tests

1. Bronchoprovocation Testing
   • Indication: For patients with normal spirometry but suspected asthma.
   • Method: Use methacholine or mannitol to induce bronchoconstriction.
   • Positive Test: ≥20% reduction in FEV₁ with standard doses.
2. Allergy Testing
   • Use: Identify allergen triggers in patients with a suggestive history.
   • Methods: Skin prick tests, specific IgE assays.
   • Significance: Supports management but not diagnostic of asthma.
3. Chest Radiography
   • Purpose: Rule out alternative diagnoses or complications in new or severe asthma cases.
   • Findings: Usually normal; may show hyperinflation, pneumomediastinum, or bronchial wall thickening.
4. Blood Tests
   • Eosinophil Count: Elevated in eosinophilic asthma; guide for biologic therapy consideration.
   • Total IgE: High levels may suggest allergic asthma or allergic bronchopulmonary aspergillosis.
5. Sputum Eosinophilia
   • Purpose: Reflect eosinophilic airway inflammation.
   • Limitations: Not routinely available in primary care.
     
     

Emerging Diagnostic Tools

1. Exhaled Nitric Oxide and Sputum Eosinophilia Combined
   • High specificity and sensitivity when used together.
2. Computed Tomography (CT)
   • Indicated in atypical cases or when ruling out structural anomalies.
     
     

Assessment During Acute Exacerbation

1. Pulse Oximetry
   • Use to monitor oxygen saturation; a drop indicates severe obstruction.
2. Arterial Blood Gas (ABG) Analysis
   • Required in severe exacerbations with suspected respiratory failure.
3. Chest X-ray
   • Indications include suspected pneumothorax, infection, or atypical presentations.
     
     

Chronic Obstructive Pulmonary Disease (COPD)

• Signs and Symptoms:
  • History of smoking or exposure to environmental pollutants.
  • Dyspnea, which may occur with or without wheezing and coughing.
  • Physical examination findings include a barrel chest, hyper-resonance to percussion, and distant breath sounds.
• Investigations:
  • Spirometry: Post-bronchodilator FEV₁/FVC ratio <70% or below the lower limit of normal (LLN).
  • Chest X-ray (CXR): Hyperinflation of the lungs and flattened diaphragm.
    
    

Chronic Rhinosinusitis

• Signs and Symptoms:
  • Persistent nocturnal cough and dyspnea from post-nasal discharge.
  • May coexist with asthma.
• Investigations:
  • Anterior rhinoscopy or nasal endoscopy: Inflammation, purulent discharge, or nasal polyps.
  • Computed tomography (CT) scan: Sinus opacification, mucosal thickening, or anatomical abnormalities.
    
    

Vocal Cord Dysfunction (Paradoxical Vocal Fold Motion)

• Signs and Symptoms:
  • Throat tightness, hoarseness, and inspiratory wheezing, especially during episodes of stress or exercise.
  • Frequently coexists with poorly controlled asthma.
• Investigations:
  • Rhinolaryngoscopy during symptomatic episodes.
  • Abnormal inspiratory flow-volume loop showing flattening.
    
    

Exercise-Induced Laryngeal Obstruction (EILO)

• Signs and Symptoms:
  • Noisy breathing, throat discomfort, and dyspnea during intense physical activity.
• Investigations:
  • Continuous laryngoscopy during exercise is the gold-standard diagnostic test.
    
    

Bronchiectasis

• Signs and Symptoms:
  • Chronic cough with copious sputum production, recurrent pulmonary infections, and wheezing.
• Investigations:
  • High-resolution CT chest: Dilated airways with bronchial wall thickening.
  • Chest X-ray: May show irregular lung markings or cystic changes in severe cases.
    
    

Congestive Heart Failure

• Signs and Symptoms:
  • Dyspnea on exertion or at rest, fatigue, dependent edema, and elevated jugular venous pressure.
• Investigations:
  • Echocardiography: Left ventricular dysfunction or preserved ejection fraction.
  • CXR: Pulmonary congestion, pleural effusions, and cardiomegaly.
    
    

Cystic Fibrosis

• Signs and Symptoms:
  • Recurrent respiratory infections, productive cough, and nasal polyps.
  • Often associated with gastrointestinal symptoms like malabsorption.
• Investigations:
  • Sweat chloride test: Diagnostic if ≥60 mmol/L.
  • Genetic testing for CFTR mutations if sweat chloride is borderline.
    
    

Gastroesophageal Reflux Disease (GERD)

• Signs and Symptoms:
  • Chronic cough, heartburn, and regurgitation.
• Investigations:
  • Improvement in respiratory symptoms with antireflux therapy.
  • Radiologic evidence of aspiration pneumonitis on CXR.
    
    

Pulmonary Embolism (PE)

• Signs and Symptoms:
  • Acute onset dyspnea, pleuritic chest pain, tachycardia, and hypoxemia.
• Investigations:
  • D-dimer levels for initial screening.
  • CT Pulmonary Angiography (CTPA): Preferred modality for confirmation.
    
    

Tracheomalacia

• Signs and Symptoms:
  • Position-dependent respiratory distress, expiratory wheezing, and stridor.
• Investigations:
  • Dynamic CT with volumetric analysis: Airway collapse during expiration.
  • Bronchoscopy: Gold standard to confirm ≥50% reduction in airway lumen.
    
    

Other Considerations

1. Pertussis:
   • Paroxysmal coughing fits with inspiratory "whoop."
   • Confirmed via nasopharyngeal swab culture or PCR testing.
2. Foreign Body Aspiration:
   • Sudden onset of unilateral wheezing or localised diminished breath sounds.
   • Confirmed via bronchoscopy or imaging (CXR, CT).
3. Eosinophilic Bronchitis:
   • Chronic non-productive cough with normal spirometry.
   • Elevated sputum eosinophils on cytological analysis.
4. Sarcoidosis:
   • Multisystem involvement with bilateral hilar lymphadenopathy on CXR.
5. Alpha-1 Antitrypsin Deficiency:
   • Early-onset COPD or emphysema in non-smokers.
   • Confirmed via serum alpha-1 antitrypsin levels.
6. Obesity:
   • Dyspnea from reduced lung compliance.
   • Diagnosis involves correlating symptoms with BMI and ruling out other conditions.
     
     

Defining Control and Uncontrolled Asthma

Complete Control of Asthma (BTS/SIGN)

• No daytime symptoms.
• No night-time awakenings due to asthma.
• No need for rescue medication.
• No asthma attacks or exacerbations.
• No limitations on activities, including exercise.
• Normal lung function (FEV₁ and/or PEF >80% predicted or personal best).
• Minimal adverse effects from medications.
  
  

Uncontrolled Asthma (NICE)

• Symptoms on three or more days per week.
• Use of SABA on three or more days per week.
• Waking at least one night per week due to asthma.
  
  

• Short-acting beta-agonists (SABA):
  • Prescribe as-needed SABA (e.g., salbutamol) to relieve acute symptoms.
  • Use is limited to patients with infrequent, short-lived wheezing and normal lung function.
  • Regular preventer therapy is usually indicated for most patients.
• Monitoring:
  • Frequent use of SABA (>2 days per week) is a red flag for inadequate control and indicates a need to step up treatment.

• Indications for Adding ICS:
  • Acute exacerbation requiring systemic corticosteroids in the past 2 years.
  • Symptoms or SABA use ≥3 times per week.
  • Waking at least once a week due to asthma.
• ICS Benefits:
  • Reduces inflammation, improves lung function, and decreases exacerbation risk.
  • Start with the lowest effective dose based on disease severity.
• Additional Notes:
  • Higher doses may be required in smokers or ex-smokers.
  • Alternatives, such as sodium cromoglicate or theophylline, may be considered if ICS is not tolerated.
    
    

1. Add a Long-Acting Beta-Agonist (LABA):
   • Combination ICS/LABA inhalers improve adherence and ensure LABA is not taken without ICS.
   • Options include:
     • Fixed-Dose Regimen: LABA + ICS + SABA as needed.
     • Maintenance and Reliever Therapy (MART): Single ICS/LABA inhaler used for both maintenance and relief.
2. Monitoring the LABA Response:
   • If symptoms improve but remain suboptimal, continue LABA and consider further steps.
   • If no improvement, discontinue LABA and assess alternatives like increasing ICS dosage or adding a leukotriene receptor antagonist (LTRA).
     
     

1. Medium-Dose ICS:
   • Increase ICS to medium-dose alongside LABA.
   • MART regimens remain an option.
2. Add-On Options:
   • LTRA: Montelukast or zafirlukast may provide additional control.
     • Monitor for potential neuropsychiatric side effects.
   • Long-Acting Muscarinic Antagonist (LAMA): Tiotropium may benefit patients who remain symptomatic.
     
     

1. High-Dose ICS:
   • Prescribe as part of a fixed-dose regimen.
   • Reliever therapy should remain a SABA.
2. Specialist-Only Options:
   • Add-on therapies, including:
     • Theophylline.
     • Biologic agents (e.g., omalizumab, mepolizumab, benralizumab, reslizumab).
   • Oral corticosteroids for severe, refractory cases.
   • Consider bronchial thermoplasty for selected patients.
     
     

• Stepping Down Treatment:
  • Gradual dose reduction every 3 months if asthma remains well controlled for at least 3 months.
  • Prioritise reducing ICS dose while maintaining other therapies.
• Annual Reviews:
  • Regular assessment using validated tools like the Asthma Control Questionnaire (ACQ) or Asthma Control Test (ACT).
• Patient Education:
  • Emphasise adherence, inhaler technique, and environmental trigger management.
    
    

1. Ensure Adherence and Technique:
   • Inhaler misuse or poor adherence can mimic treatment failure.
   • Review technique at every consultation.
2. Address Comorbidities and Triggers:
   • Smoking, allergens, and occupational exposures may worsen control.
   • Treat underlying conditions like gastroesophageal reflux disease (GORD) or chronic rhinosinusitis.
3. Personalize Treatment:
   • Balance control with minimising side effects.
   • Tailor therapy to patient preferences and lifestyle.
     
     

Long-term Effects

1. Airway Remodeling and Lung Function:
   • In asthma, structural airway changes, termed airway remodeling, are often independent of airway inflammation and may not respond to anti-inflammatory medications like inhaled corticosteroids (ICS).
   • Evidence from longitudinal studies indicates that children with persistent asthma experience early deficits in lung function growth, primarily by ages 6–9 years, with minimal further decline in adulthood unless severe exacerbations are frequent.
   • Adults with asthma generally display stable lung function phenotypes, but severe chronic asthma with repeated exacerbations can lead to an accelerated decline in lung function and fixed airflow obstruction.
     
     

Mortality and Life Expectancy

1. Mortality Risks:
   • Asthma mortality is closely associated with lung function. Individuals with forced expiratory volume in 1 second (FEV₁) in the lowest quartile experience an 8-fold increase in mortality risk.
   • Contributing factors to increased mortality include:
     • Inadequate asthma management.
     • Age >40 years.
     • Smoking history (>20 pack-years).
     • Blood eosinophilia and FEV₁ values of 40–69% of predicted.
2. Life Expectancy:
   • For individuals with well-controlled asthma, life expectancy is similar to that of the general population.
   • Protective factors include maintaining physical activity levels, while risks are higher among males, those with hypertension, and those with poor socioeconomic conditions.

Remission

1. Possibility of Remission:
   • Modern therapies, such as biologics and allergen immunotherapies, have made remission an achievable outcome. Criteria for remission include:
     • No exacerbations or hospitalisations.
     • Stable pulmonary function and minimal reliever use.
     • Continued low-dose ICS or other controller therapy.
2. Remission Trends:
   • Nearly 50% of children diagnosed with asthma show symptom reduction and decreased medication needs by late adolescence or early adulthood, while those diagnosed later in life often have persistent symptoms.
     
     

Social Determinants and Disparities

1. Impact of Socioeconomic and Environmental Factors:
   • Social determinants, including inadequate housing, exposure to indoor and outdoor pollutants, and limited healthcare access, profoundly affect asthma outcomes.
   • In the U.S., racial and ethnic minorities and those living in poverty experience higher asthma-related morbidity and mortality rates, often due to reduced healthcare access.
2. Economic Burden:
   • Asthma contributes to approximately 100 million restricted activity days annually and accounts for 500,000 hospitalisations yearly, with children comprising 40% of cases.
   • Annual expenditures for asthma and chronic obstructive pulmonary disease (COPD) healthcare utilisation exceed $82 billion.
     
     

Chronic Symptoms and Complications

1. Irreversible Changes and Disease Progression:
   • Poorly controlled asthma over time leads to irreversible airway remodeling, which contributes to persistent airflow obstruction.
   • While many patients achieve good control with therapy, a subset experiences chronic symptoms, particularly those with late-onset asthma or frequent exacerbations.

Disease-Related Complications

1. Airway Remodeling
   • Persistent inflammation leads to structural airway changes and irreversible obstruction.
   • Associated with long-term activity limitations and reduced quality of life.
2. Severe Exacerbations
   • Triggered by major exposures such as allergens or NSAIDs in sensitive individuals.
   • Requires urgent medical intervention to prevent respiratory failure.
3. Moderate Exacerbations
   • Commonly triggered by infections or allergen exposure.
   • Manageable with oral corticosteroids, inhaled corticosteroids, and as-needed beta agonists.
4. Obstructive Sleep Apnea
   • Poor asthma control may worsen sleep-disordered breathing.
5. Respiratory Arrest
   • Life-threatening complication of uncontrolled exacerbations.
6. Pneumothorax
   • Rupture of lung tissue causing air leakage into the pleural cavity.
7. Aspiration
   • Increased risk during severe exacerbations, complicating recovery.
8. Decline in Lung Function
   • Chronic inflammation and remodeling contribute to progressive airflow limitation.
     
     

Complications Related to Corticosteroid Use

1. Oral Candidiasis (Thrush)
   • Common; preventable with proper inhaler technique, a spacer, and mouth rinsing.
2. Dysphonia
   • Hoarseness caused by laryngeal muscle spasm; mitigated by correct inhaler use.
3. Oesophageal Candidiasis
   • Rare; requires antifungal treatment and reassessment of inhaler technique.
     
     

1. Osteoporosis and Fractures
   • Long-term systemic corticosteroid use reduces bone density.
2. Hypertension and Diabetes
   • Prolonged exposure increases blood pressure and glucose intolerance.
3. Adrenal Suppression
   • Chronic steroid use impairs adrenal gland function, requiring tapering during discontinuation.
4. Mood Disorders
   • Associated with anxiety, depression, and mood swings.
5. Infections
   • Immunosuppression elevates susceptibility to bacterial, viral, and fungal infections.
6. Cataracts and Glaucoma
   • Ocular complications from prolonged corticosteroid use.
7. Peptic Ulcer Disease
   • Increased risk of gastrointestinal ulceration with long-term use.
     
     

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